# The role of programmed cell death 1 in autoimmune diseases: mechanisms and therapeutic implications

## TL;DR

This paper reviews how the PD-1 gene influences autoimmune diseases and explores potential therapies targeting its signaling pathway.

## Contribution

The paper systematically analyzes PD-1's role in autoimmune diseases and highlights novel therapeutic strategies involving PD-1/PD-L1 signaling.

## Key findings

- Abnormal PD-1 gene expression and signaling contribute to immune system overactivation in autoimmune diseases.
- Therapies targeting PD-1/PD-L1 binding may restore immune balance and improve patient outcomes.
- Vγ4γδT cells could serve as a new target for PD-1-based monitoring and treatment.

## Abstract

Autoimmune diseases are complex disorders caused by the interaction between the immune system and self-antigens, involving genetic, environmental triggers, and other cellular factors. The programmed cell death receptor-1 (PD-1) gene, as a critical factor in immune regulation, has garnered significant attention in the study of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis. Although the pathogenesis of these diseases varies, they all manifest as a breakdown in immune tolerance and an imbalance in immune homeostasis. Research has shown that in the development of autoimmune diseases, changes in PD-1 gene expression, its binding with PD-L1 and PD-L2, and signal transduction pathways are often abnormal. These abnormalities may lead to the overactivation of T cells and B cells, resulting in the attack on self-tissues. Consequently, therapeutic strategies targeting the PD-1/PD-L1 signaling pathway hold promising potential. Gene therapy approaches or small-molecule drugs that enhance PD-L1 transcription could strengthen PD-1/PD-L1 binding and restore inhibitory signaling, thereby rebalancing immune responses and improving patients’ quality of life. Additionally, recent studies suggest that targeting Vγ4γδT cells to monitor disease progression and prognosis represents another potential PD-1-based therapeutic strategy. This review focuses on the role of the PD-1 gene in autoimmune diseases, systematically elaborating on the structure, molecular functions, and regulatory mechanisms of PD-1 and its ligands, while providing an in-depth analysis of PD-1’s mechanistic involvement in autoimmune diseases and its therapeutic prospects.